Plasma homocysteine (Hcy) is an independent risk factor for Age related macular degeneration (AMD) and an inducer of inflammation. Homocysteine catabolism releases hydrogen sulfide (H₂S). H₂S has controversial effects on inflammation. In this study we have analysed the endogenous and exogenous H₂S in modulating inflammation using adult retinal pigment epithelial (ARPE-19) cells as an in vitro model for AMD. ARPE-19 cells were treated with various concentrations of Hcy (15, 30 and 50 μM) for 3 h. Expression of Hcy transulfuration genes (CBS, CSE) by qPCR and western blot. H₂S levels were measured using Free Radical Analyzer System (WPI, USA). The inflammatory markers (IL-6 and IL-8) were evaluated using real-time PCR and ELISA. Hcy exposure increased CBS protein expression, hydrogen sulfide levels and pro-inflammatory cytokines, modulating CBS by silencing did not alter H₂S levels, but inhibition of CSE with PAG inhibited H₂S production and decreased cytokine (IL-6 and IL-8) levels. On the contrary exogenous supply of hydrogen sulfide with NaHS and by compound 1c showed anti-inflammatory effects even in the presence of Hcy. This study shows that exogenous delivery of H₂S decreases inflammation in retinal pigment epithelial cells on exposure to Hcy in ARPE-19 cells.

血浆同型半胱氨酸 (Hcy) 是年龄相关性黄斑变性 (AMD) 的独立危险因素和炎症诱导剂。同型半胱氨酸分解代谢释放硫化氢 (H ₂ S)。H ₂ S 对炎症具有有争议的影响。在这项研究中，我们使用成人视网膜色素上皮 (ARPE-19) 细胞作为AMD 的体外模型分析了内源性和外源性 H ₂ S 在调节炎症中的作用。ARPE-19 细胞用不同浓度的 Hcy（15、30 和 50 μM）处理 3 小时。通过 qPCR 和蛋白质印迹表达 Hcy 转硫基因（CBS、CSE）。H ₂使用自由基分析仪系统（WPI，美国）测量 S 水平。使用实时 PCR 和 ELISA 评估炎症标志物（IL-6 和 IL-8）。Hcy 暴露增加了 CBS 蛋白表达、硫化氢水平和促炎细胞因子，通过沉默调节 CBS 不会改变 H ₂ S 水平，但用 PAG 抑制 CSE 抑制了 H ₂ S 产生并减少了细胞因子（IL-6 和 IL-8 ) 水平。相反，外源性硫化氢与 NaHS 和化合物 1c 的供应即使在 Hcy 存在下也显示出抗炎作用。该研究表明，在 ARPE-19 细胞中，H ₂ S 的外源性递送减少了视网膜色素上皮细胞在暴露于 Hcy 时的炎症。